The detection and treatment of cancerous tissue has been the subject of intense investigation for many years. One among the many approaches to its detection has concerned the identification of tumor specific antigens. Where these antigens can be identified, radionucleid labeled antibodies have been employed which tend to collect at tumor sites. When so concentrated, somewhat elaborate radiation detection equipment then is employed to record, for example, by imaging the concentrations of the emissive substances and thus to locate neoplastic tissue. Important advances in this procedure have been evidenced through the use of monoclonal antibodies or fragments thereof with a variety of radionucleides. Typical techniques for carrying out imaging of the antibodies have involved, for example, tomographic scanning, immunoscintigraphy and the like. The particular choice of radionucleid for labeling antibodies is dependent upon its nuclear properties, the physical half life, the detection instrument capabilities, the pharmacokinetics of the radiolabeled antibody, and the degree of difficulty of the labeling procedure. The most widely used of these radionucleides in nuclear medicine imaging include technetium, Tc.sup.99m, iodine I.sup.123, I.sup.131, and indium In.sup.111. Of the above, for localizing tumors of the gastro-intestinal tract, the radionucleid I.sup.131 is used as the marker or label in conjunction with imaging gamma cameras and the like which are relatively large and elaborate devices positioned above the patient during the imaging process.
In spite of its somewhat extensive utilization, I.sup.131 is not an ideal radionucleid for use in diagnostic medicine. The high energy gamma-photon emitted from I.sup.131 is poorly detected by classic gamma camera and like instrumentation. In addition, the particular admissions of emissions deliver a high radiation dose to the patient. Further, the imaging definition of these external imaging devices have not been satisfactory for many reasons. As tumor sites become smaller, the radionucleid concentrations thereat will tend to be lost, from an imaging standpoint, in the background or blood pool radiation necessarily present in the patient.
Over the recent past, a surgical procedure has been developed concerning the differentiation and removal of such neoplastic tissue through the use of much lower energy gamma emission labels for example, I.sup.125 (27-35 kev). While such a radiolabel cannot be employed with conventional external imaging or scanning devices, it has been found that when employed with a probe type detection structure, a highly effective differentiation technique can be evolved. More particularly, the longer half life of this type of radiolabel coupled with a surgical methodology involving the waiting of appropriate intervals from the time of introduction of the radiolabelled inantibody to the patient to the time of surgery, can evolve a highly accurate differentiation of cancerous tumor. This improved method of localization, differentiation and removal of cancerous tumor involves a surgical procedure wherein the patient suspected of containing neoplastic tissue is administered an effective amount of a labeled antibody specific for neoplastic tissue and labeled with a radioactive isotope as above-noted exhibiting photon emissions of specific energy levels. Next, the surgical procedure is delayed for a time interval following such administration for permitting the labeled antibody to preferentially concentrate in any neoplastic tissue present in the patient so as to increase the ratio of photon emissions from the neoplastic tissue to the background photon emissions. Thereafter, an operative field of the patient is surgically accessed and tissue within the operative field to be examined for neoplastic tissue has the background photon emission count determined. Once the background photon emission count for the tissue within the operative field has been determined, this hand-held probe is manually positioned within the operative field adjacent tissue suspected of being neoplastic. Readouts then can be achieved from probe counting for differentiation. In the above regard, reference is made to the following technical publications:
I. "CEA-Directed Second-Look Surgery in the Asymptomatic Patient after Primary Resection of Colorectal Carcinoma", E. W. Martin, Jr., MD, J. P. Minton, MD, PhD, Larry C. Carey, MD. Annals of Surgery 202: 1 (September 1985 301-12. PA1 II. "Intraoperative Probe-Directed Immunodetection Using a Monoclonal Antibody", P. J. O'Dwyer, MD, C. M. Mojzsik, RN MS, G. H. Hinkle, RPh, MS, M. Rousseau, J. Olsen, MD, S. E. Tuttle, MD, R. F. Barth, PhD, MO. Thurston, PhD, D. P. McCabe, MD, W. B. Farrar, MD, E. W. Martin, Jr., MD. Archives of Surgery, 121 (December 1986) 1321-1394. PA1 III. "Intraoperative Radioimmunodetection of Colorectal Tumors with a Hand-Held Radiation Detector", D. T. Martin, MD, G. H. Hinkle, MS RPh, S. Tuttle, MD, J. Olsen, MD, H. Abdel-Nabi, MD, D. Houchens, PhD, M. Thurston, PhD, E. W. Martin, Jr., MD. American Journal of Surgery, 150: 6 (December 1985) 672-75. PA1 IV. "Portable Gamma Probe for Radioimmune Localization of Experimental Colon Tumor Xenografts", D. R. Aitken MD, M. O. Thurston, PhD, G. H. Hinkle, MS RPh, D. T. Martin, MD, D. E. Haagensen, Jr., MD, PhD, D. Houchens, PhD, S. E. Tuttle, MD, E. W. Martin, Jr., MD. Journal of Surgical Research, 36: 5 (1984) 480-489. PA1 V. "Radioimmunoguided Surgery: Intraoperative Use of Monoclonal Antibody 17-1A in Colorectal Cancer". E. W. Martin, Jr., MD, S. E. Tuttle, MD, M. Rousseau, C. M. Mojzisik, RN MS, P. J. O'Dwyer, MD, G. H. Hinkle, MS RPh, E. A. Miller, R. A. Goodwin, O. A. Oredipe, MA, R. F. Barth, MD, J. O. Olsen, MD, D. Houchens, PhD, S. D. Jewell, MS, D. M. Bucci, BS, D. Adams, Z. Steplewski, M. O. Thurston, PhD, Hybridoma 5 Suppl 1 (1986) S97-108.
Reference further is made to commonly assigned application for U.S. patent Ser. No. 06/905,880 entitled "Method for Locating, Differentiating, and Removing Neoplasms" by Edward W. Martin, Jr., and Marlin O. Thurston, filed Sept. 10, 1986.
The success of this highly effective differentiation and localization technique is predicated upon the availability of a probe-type detecting device capable of detecting extemely low amounts of radiation necessarily developed with the procedure. In this regard, low energy radionucleides are used such as I.sup.125 and the distribution of radiolabeled antibody with the nucleid is quite sparse so that background emissions can be minimized and the ratio of tumor-specific counts received to background counts can be maximized. Conventional radiation detection probe-type devices are ineffective for this purpose. Generally, because a detection device is required for the probes which is capable of performing at room temperatures, a detection crystal such as cadmium telluride is employed. The probe using such a crystal must be capable of detecting as little as a single gamma ray emission which may, for example, create electron-hole pairs in the crystal of between about 2,000 and 4,000 electrons. Considering that an ampere generates 6.25.times.10.sup.18 electrons per second, one may observe that extremely small currents must be detectable with such probe. However, the probe system also must be capable of discriminating such currents from any of a wide variety of electrical disturbances, for example which may be occasioned from cosmic inputs, room temperature molecular generated noise and capacitively induced noise developed from the mere manipulation of the probe itself. While being capable of performing under these extreme criteria, the same probe further must be capble of performing under the requirements of the surgical theater. In this regard, it must be sterilizable and rugged enough to withstand manipulation by the surgeon within the body cavity of the patient. Further, the system with which the probe is employed, must be capable of perceptively apprising the surgeon of when neoplastic tissue is being approached such that the device may be employed for the purpose of guiding the surgeon to the situs of cancer. Finally, for surgical use, the probe instrument must be small, so as to be effectively manipulated through surgical openings and the like. Such dimunitive size is not esily achieved under the above operational criteria. This technique has been described as "radioimmuno-guided surgery", a surgical approach developed by E. W. Martin, Jr., MD, and M. O. Thurston, PhD.